Lineage-Specific Telomere Shortening and Unaltered Capacity for Telomerase Expression in Human T and B Lymphocytes with Age
Abstract
Age effects on telomere length and telomerase expression in peripheral blood lymphocytes were analyzed from 121 normal individuals age newborn to 94 years and revealed several new findings. 1) Telomere shortening was observed in CD4+ and CD8+ T and B cells with age. However, the rate of telomere loss was significantly different in these populations, 35 ± 8, 26 ± 7, and 19 ± 7 bp/year for CD4+ and CD8+ T and B cells, respectively. In addition, CD4+ T cells had the longest average telomeres at all ages, followed by B cells, with CD8+ T cell telomeres the shortest, suggesting that these lymphocyte populations may have different replicative histories in vivo. 2) Telomerase activity in freshly isolated T and B cells was indistinguishably low to undetectable at all ages but was markedly increased after Ag and costimulatory receptors mediated stimulation in vitro. Furthermore, age did not alter the magnitude of telomerase activity induced after stimulation of T or B lymphocytes through Ag and costimulatory receptors or in response to PMA plus ionomycin treatment. 3) The levels of telomerase activity induced by in vitro stimulation varied among individual donors but were highly correlated with the outcome of telomere length change in CD4+ T cells after Ag receptor-mediated activation. Together, these results indicate that rates of age-associated loss of telomere length in vivo in peripheral blood lymphocytes is specific to T and B cell subsets and that age does not significantly alter the capacity for telomerase induction in lymphocytes.
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Cross-sectional analyses demonstrate progressive shortening of telomere length with advancing age in leukocytes or peripheral blood mononuclear cells, as well as in isolated granulocytes and lymphocytes (CD4 and CD8 T cells, and B cells).
“Cross-sectional analyses demonstrate progressive shortening of TL IN with advancing age in leukocytes or peripheral blood mononuclear cells (PBMCs), as well as in isolated granulocytes and lymphocytes (CD4 and CD8 T cells, and B cells) [227].”
From Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy (2024) · cites this paper as [227]
Telomere length is a more direct marker of replicative history.
“A more direct marker of replicative history is telomere length”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Son et al., 2000
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- Authors
- Son, N. H., Murray, S., Yanovski, J., Hodes, R. J., & Weng, N.-P.
- Affiliations
- National Institute on Aging (US)
- National Institutes of Health (US)
- Corresponding author
- Murray, Shannon
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-08-01
- Volume
- 165
- Issue
- 3
- Pages
- 1191-1196
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2142865919
- Cited by
- 200
- References
- 46
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 12 · 2016: 6 · 2015: 7 · 2014: 11 · 2013: 12 · 2012: 9
- FWCI
- 7.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- NSUWorks (Nova Southeastern University) (submittedVersion)
- Funders
- Johns Hopkins University
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- telomere shortening, telomerase activity, aging, T cells, B cells, CD4+ T cells, CD8+ T cells, telomere length, costimulatory receptors, lymphocyte subsets
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, B-Lymphocytes, Cell Division, Cells, Cultured, Child, Child, Preschool, Enzyme Activation, Humans, Infant, Infant, Newborn, Middle Aged, T-Lymphocytes, CD4-Positive T-Lymphocytes, Telomere, CD8-Positive T-Lymphocytes, Antigens, CD19, Cell Lineage, Telomerase
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